Covalently closed circular of supercoiled DNA has become a topic of considerable interest in the field of molecular biology as a result of both of its unique structural properties and its presence in a wide variety of biological locations. As a result of its appearance in the "life cycle" of various DNA and RNA tumor viruses, supercoiled DNA is especially relevant to current problems in viral oncogenicity. Using a wide variety of experimental approaches we and other investigators have concluded that superhelical DNA contains altered or interrupted secondary structure. In the case of SV40 and polyoma DNA the evidence strongly supports the appearance of unpaired bases at localized sites. The major focus of our research program centers on the structural details and role of unpaired regions in biological function. In particular, we are directly concerned with the expression of viral messenger RNA from supercoiled DNA. In addition we would like to obtain an understanding of recombination with regard to circular DNA since this is an essential event for the integration of the viral genome into a host cell chromosome. The latter occurs with simian virus 40 producing stable transformed tumor cells. Consequently this system represents an excellent model for the development of our understanding of the events leading to viral induced cancer. The experimental approaches center upon the carbodiimide modification of SV40 DNA. In particular in vitro transcription, analysis of DNA binding proteins and hydrodynamic studies will be performed on SV40 and modified SV40 DNA to elucidate mechanisms of gene expression and control.